Effects of verapamil SR and atenolol on 24-hour blood pressure and heart rate in hypertension patients with coronary artery disease: an international verapamil SR-trandolapril ambulatory monitoring substudy

Scott J Denardo, Yan Gong, Rhonda M Cooper-DeHoff, Csaba Farsang, Matyas Keltai, László Szirmai, Franz H Messerli, Anthony A Bavry, Eileen M Handberg, Giuseppe Mancia, Carl J Pepine, Scott J Denardo, Yan Gong, Rhonda M Cooper-DeHoff, Csaba Farsang, Matyas Keltai, László Szirmai, Franz H Messerli, Anthony A Bavry, Eileen M Handberg, Giuseppe Mancia, Carl J Pepine

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 registration: ClinicalTrials.gov NCT00133692.

Conflict of interest statement

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.

Figures

Fig 1. Consort diagram showing selection of…
Fig 1. Consort diagram showing selection of INVEST patients for the ambulatory monitoring substudy analysis.
The subgroup consisted of 141 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment. Patients were excluded if their blood pressure and heart rate recordings did not meet the criteria for inclusion (adequate technical quality ≥85% of the 24-hour recording period,

Fig 2. Office-based and 24-hour ambulatory monitoring…

Fig 2. Office-based and 24-hour ambulatory monitoring systolic blood pressure (SBP), diastolic blood pressure (DBP),…

Fig 2. Office-based and 24-hour ambulatory monitoring systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) at baseline and following 1 year of treatment.
The baseline data contain both verapamil SR- and atenolol-based strategies combined, while the data following 1 year of treatment is individualized to treatment strategy. For comparison, baseline office-based data for the remaining INVEST patients, who did not have ambulatory blood pressure monitoring, are shown to the left. Horizontal line through each box represents median; bottom and top of box represent first and third quartiles; the whiskers represent minimum and maximum of all data.

Fig 3. Office-based systolic and diastolic blood…

Fig 3. Office-based systolic and diastolic blood pressure based upon treatment strategy among 423 frequency-matched…

Fig 3. Office-based systolic and diastolic blood pressure based upon treatment strategy among 423 frequency-matched INVEST patients who did not have ambulatory blood pressure monitoring.
The minimum P values were 0.12 and 0.09, respectively.

Fig 4. Twenty-four-hour ambulatory systolic blood pressure…

Fig 4. Twenty-four-hour ambulatory systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate…

Fig 4. Twenty-four-hour ambulatory systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate by strategy, both at baseline and after 1 year of treatment.
Individual data points represent mean values. Nighttime dipping was determined over the time interval 20:00–02:00 and morning surge over the interval 02:00–10:00.
Fig 2. Office-based and 24-hour ambulatory monitoring…
Fig 2. Office-based and 24-hour ambulatory monitoring systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) at baseline and following 1 year of treatment.
The baseline data contain both verapamil SR- and atenolol-based strategies combined, while the data following 1 year of treatment is individualized to treatment strategy. For comparison, baseline office-based data for the remaining INVEST patients, who did not have ambulatory blood pressure monitoring, are shown to the left. Horizontal line through each box represents median; bottom and top of box represent first and third quartiles; the whiskers represent minimum and maximum of all data.
Fig 3. Office-based systolic and diastolic blood…
Fig 3. Office-based systolic and diastolic blood pressure based upon treatment strategy among 423 frequency-matched INVEST patients who did not have ambulatory blood pressure monitoring.
The minimum P values were 0.12 and 0.09, respectively.
Fig 4. Twenty-four-hour ambulatory systolic blood pressure…
Fig 4. Twenty-four-hour ambulatory systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate by strategy, both at baseline and after 1 year of treatment.
Individual data points represent mean values. Nighttime dipping was determined over the time interval 20:00–02:00 and morning surge over the interval 02:00–10:00.

References

    1. Fagard RH, Thijs L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer DA. Prognostic significance of ambulatory blood pressure in hypertensive patients with history of cardiovascular disease. Blood Press Monit. 2008;13: 325–332. 10.1097/MBP.0b013e32831054f5
    1. Hansen TW, Li Y, Boggia J, Thijs L, Richart T, Staessen JA. Predictive role of the nighttime blood pressure. Hypertension. 2011;57: 3–10. 10.1161/HYPERTENSIONAHA.109.133900
    1. Fagard RH, Celis H, Thijs L, Staessen JA, Clement DL, De Buyzere ML, et al. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension. 2008;51: 55–61.
    1. Staessen JA, Thijs L, Fagard R, O'Brien ET, Clement D, de Leeuw PW, et al. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators. JAMA. 1999;282: 539–546.
    1. Dolan E, Stanton A, Thijs L, Hinedi K, Atkins N, McClory S, et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension. 2005;46: 156–161.
    1. Kikuya M, Ohkubo T, Asayama K, Metoki H, Obara T, Saito S, et al. Ambulatory blood pressure and 10-year risk of cardiovascular and noncardiovascular mortality: the Ohasama study. Hypertension. 2005;45: 240–245.
    1. Hansen TW, Thijs L, Boggia J, Li Y, Kikuya M, Björklund-Bodegård K, et al. International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes Investigators. Prognostic value of ambulatory heart rate revisited in 6928 subjects from 6 populations. Hypertension. 2008;52: 229–235. 10.1161/HYPERTENSIONAHA.108.113191
    1. Mancia G, Parati G, Hennig M, Flatau B, Omboni S, Glavina F, et al. ELSA Investigators. Relation between blood pressure variability and carotid artery damage in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis (ELSA). J Hypertens. 2001;19: 1981–1989.
    1. Sega R, Corrao G, Bombelli M, Beltrame L, Facchetti R, Grassi G, et al. Blood pressure variability and organ damage in a general population: results from the PAMELA Study. Hypertension. 2002;39: 710–714.
    1. Kikuya M, Hozawa A, Ohokubo T, Tsuji I, Michimata M, Matsubara M, et al. Prognostic significance of blood pressure and heart rate variabilities: the Ohasama Study. Hypertension. 2000;36: 901–906.
    1. Pierdomenico SD, Lapenna D, Di Tommaso R, Di Carlo S, Esposito AL, Di Mascio R, et al. Blood pressure variability and cardiovascular risk in treated hypertensive patients. Am J Hypertens. 2006;19: 991–997.
    1. Hansen TW, Thijs L, Li Y, Boggia J, Kikuya M, Björklund-Bodegård K, et al. International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes Investigators. Prognostic value of reading-to-reading blood pressure variability over 24 hours in 8938 subjects from 11 populations. Hypertension. 2010;55: 1049–1057. 10.1161/HYPERTENSIONAHA.109.140798
    1. Rothwell PM. Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension. Lancet. 2010;375: 938–948. 10.1016/S0140-6736(10)60309-1
    1. Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Gattobigio R, Guerrieri M, et al. Altered circadian blood pressure profile and prognosis. Blood Press Monit. 1997;2: 347–352.
    1. Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli, et al. Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension. 1994;24: 793–801.
    1. Brotman DJ, Davidson MB, Boumitri M, Vidt DG. Impaired diurnal blood pressure variation and all-cause mortality. Am J Hypertens. 2008;21: 92–97.
    1. Ohkubo T, Imai Y, Tsuji I, Nagai K, Watanabe N, Minami N, et al. Relation between nocturnal decline in blood pressure and mortality. The Ohasama Study. Am J Hypertens. 1997;10: 1201–1207.
    1. Ben-Dov IZ, Kark JD, Ben-Ishay D, Mekler J, Ben-Arie L, Bursztyn M. Blunted heart rate dip during sleep and all-cause mortality. Arch Intern Med. 2007;167: 2116–2121.
    1. Verdecchia P, Angeli F, Mazzotta G, Garofoli M, Ramundo E, Gentile G, et al. Day-night dip and early-morning surge in blood pressure in hypertension: prognostic implications. Hypertension. 2012;60: 34–42. 10.1161/HYPERTENSIONAHA.112.191858
    1. Li Y, Thijs L, Hansen TW, Kikuya M, Boggia J, Richart T, et al. International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes Investigators. Prognostic value of the morning blood pressure surge in 5645 subjects from 8 populations. Hypertension. 2010;55: 1040–1048. 10.1161/HYPERTENSIONAHA.109.137273
    1. Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C, et al. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med. 1985;313: 1315–1322.
    1. Willich SN, Levy D, Rocco MB, Tofler GH, Stone PH, Muller JE. Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study population. Am J Cardiol. 1987;60: 801–806.
    1. Marler JR, Price TR, Clark GL, Muller JE, Robertson T, Mohr JR, et al. Morning increase in onset of ischemic stroke. Stroke. 1989;20: 473–476.
    1. Kario K, Pickering TG, Umeda Y, Hoshide S, Hoshide Y, Morniari M, et al. Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study. Circulation. 2003;107: 1401–1406.
    1. White WB. Cardiovascular risk and therapeutic intervention for the early morning surge in blood pressure and heart rate. Blood Press Monit. 2001;6: 63–72.
    1. Hermida RC, Ayala DE, Fernández JR, Portaluppi F, Fabbian F, Smolensky MH. Circadian rhythms in blood pressure regulation and optimization of hypertension treatment with ACE inhibitor and ARB medications. Am J Hypertens. 2011;24: 383–391. 10.1038/ajh.2010.217
    1. Webb AJ, Fischer U, Mehta Z, Rothwell PM. Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis. Lancet. 2010;375: 906–915. 10.1016/S0140-6736(10)60235-8
    1. Zhang Y, Agnoletti D, Safar ME, Blacher J. Effect of antihypertensive agents on blood pressure variability: the Natrilix SR versus candesartan and amlodipine in the reduction of systolic blood pressure in hypertensive patients (X-CELLENT) study. Hypertension. 2011;58: 155–160. 10.1161/HYPERTENSIONAHA.111.174383
    1. Shimada K, Ogihara T, Saruta T, Kuramoto K; REZALT Study Group. Effects of combination olmesartan medoxomil plus azelnidipine versus monotherapy with either agent on 24-hour ambulatory blood pressure and pulse rate in Japanese patients with essential hypertension: additional results from the REZALT study. Clin Ther. 2010;32: 861–881. 10.1016/j.clinthera.2010.04.020
    1. Hermida RC, Ayala DE. Chronotherapy with the angiotensin-converting enzyme inhibitor ramipril in essential hypertension: improved blood pressure control with bedtime dosing. Hypertension. 2009;54: 40–46. 10.1161/HYPERTENSIONAHA.109.130203
    1. Pepine CJ, Handberg-Thurmond E, Marks RG, Conlon M, Cooper-DeHoff R, Volkers P, et al. Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): an Internet-based randomized trial in coronary artery disease patients with hypertension. J Am Coll Cardiol. 1998;32: 1228–1237.
    1. Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH, et al. INVEST Investigators. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA. 2003;29: 2805–2816.
    1. Bilo G, Giglio A, Styczkiewicz K, Caldara G, Maronati A, Kawecka-Jaszcz K, et al. A new method for assessing 24-h blood pressure variability after excluding the contribution of nocturnal blood pressure fall. J Hypertens. 2007;25: 2058–2066.
    1. Mancia G. Short-and long-term blood pressure variability: present and future. Hypertension. 2012;60: 512–517. 10.1161/HYPERTENSIONAHA.112.194340
    1. Leary AC, Struthers AD, Donnan PT, MacDonald TM, Murphy MB. The morning surge in blood pressure and heart rate is dependent on levels of physical activity after waking. J Hypertens. 2002;20: 865–870.
    1. Vollmer WM, Appel LJ, Svetkey LP, Moore TJ, Vogt TM, Conlin PR, et al. DASH Collaborative Research Group. Comparing office-based and ambulatory blood pressure monitoring in clinical trials. J Hum Hypertens. 2005;19: 77–82.
    1. Hodgkinson J, Mant J, Martin U, Guo B, Hobbs FD, Deeks JJ, et al. Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: systematic review. BMJ. 2011;342: d3621 10.1136/bmj.d3621
    1. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311: 507–520. 10.1001/jama.2013.284427
    1. Omboni S, Parati G, Palatini P, Vanasia A, Muiesan ML, Cuspidi C, et al. Reproducibility and clinical value of nocturnal hypotension: prospective evidence from the SAMPLE study. Study on Ambulatory Monitoring of Pressure and Lisinopril Evaluation. J Hypertens. 1998;16: 733–738.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa