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Randomized study of traditional versus aggressive systolic blood pressure control (Cardio-Sis): rationale, design and characteristics of the study population

Journal of Human Hypertension volume 22, pages 243–251 (2008)Cite this article

Abstract

The hypothesis that a therapeutic strategy aimed at lowering systolic blood pressure (SBP) below 130 mm Hg is superior to a conventional strategy targeted at below 140 mm Hg in hypertensive subjects has never been tested in randomized intervention studies. The Studio Italiano Sugli Effetti Cardiovascolari del Controllo della Pressione Arteriosa Sistolica (Cardio-Sis) is a multi-centre study in non-diabetic, treated hypertensive subjects aged >55 years with uncontrolled SBP (⩾150 mm Hg) and at least one additional cardiovascular risk factor (ClinicalTrials.gov identifier: NCT00421863). Subjects are randomized to an SBP goal <140 mm Hg (conventional) or <130 mm Hg (aggressive), independently of baseline and achieved diastolic blood pressure (BP). Anti-hypertensive drugs dispensed for the study are restricted to a list of specific drugs. The primary outcome of the study is based on regression of left ventricular hypertrophy (LVH) using electrocardiography (ECG). The hypothesis is that subjects without LVH regression or with new development of LVH 2 years after randomization are 19% with conventional strategy and 12% with aggressive strategy. Secondary outcome is a composite pool of pre-specified fatal and non-fatal events. Randomization of 1111 subjects was completed by February 2007. Mean age of subjects (41% men) at entry was 67 years. BP was 158/87 mm Hg (systolic/diastolic) and prevalence of LVH by ECG was 21.0%. Cardio-Sis is the first randomized study specifically designed to compare two different SBP goals. Results will be broadly applicable to subjects with uncontrolled SBP under anti-hypertensive treatment.

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Acknowledgements

The study was partially supported by an unrestricted grant from Boehringer-Ingelheim, Sanofi-Aventis and Pfizer. Study drugs were provided by Boehringer-Ingelheim, Sanofi-Aventis, Pfizer, Bayer and Merk (Darmstadt).

Author information

Author notes

  1. Struttura Complessa di Cardiologia, Unità di Ricerca Clinica—Cardiologia Preventiva, Ospedale S Maria della Misericordia, Perugia, Italy

  2. Dr P Verdecchia, 1Struttura Complessa di Cardiologia, Unità di Ricerca Clinica—Cardiologia Preventiva, Ospedale S Maria della Misericordia, Piazzale G Menghini, Perugia 06132, Italy. E-mail: verdec@tin.it

Consortia

Cardio-Sis Study Group (see appendix)

Appendix

Appendix

Steering committee

Paolo Verdecchia (Chairman), Jan A Staessen, Augusto Achilli, Giovanni de Simone, Antonello Ganau, Gianfrancesco Mureddu, Sergio Pede.

Adjudication committee

Carlo Porcellati and Giovanni Fornari.

Coordinating centre

ANMCO Research Centre (Aldo P Maggioni, Martina Ceseri, Donata Lucci, Andrea Lorimer)

ECG reading centre

Associazione Umbra Cuore e Ipertensione (Salvatore Repaci, Claudia Castellani, Paola Achilli, Carla Jaspers).

Clinical record from online management

Clinical Research Technology (Giovanni Cucchiara, Carlo Panzano).

Clinical help online

Fabio Angeli.

Participating centres

Aosta (C Aillon, MG Sclavo), Benevento (M Scherillo, D Raucci, M Di Donato), Brescia (L Dei Cas, P Faggiano), Cagliari Brotzu (M Porcu, R Calamida, L Pistis), Caltanissetta (F Vancheri, M Alletto, M Curcio), Casarano (G Pettinati, M Ieva, A Muscella), Castiglione del Lago (M Guerrieri, C Denbek), Catania Garibaldi-Nesima (M Gulizia, GM Francese), Catanzaro (F Perticone, G Iemma), Chiari (R Fariello, N Sala), Chieti (A Mezzetti, SD Pierdomenico, M Bucci), Città della Pieve (G Benemio, R Gattobigio, N Sacchi), Città di Castello Cardiologia (M Cocchieri, L Prosciutti), Città di Castello Medicina (P Battocchi, O Garognoli, G Arcelli), Cremona (S Pirelli, C Emanuelli), Erice (GB Braschi, M Abrignani), Genova DIMI (G De Ferrari, R Pontremoli), Gorizia (D Igidbashian, R Marini, L Scarpino), Gubbio (S Mandorla, M Buccolieri, L Picchi), Lido di Camaiore (G Casolo, M Pardini, G Marracci), Napoli Policlinico Federico II (P Strazzullo, F Galletti, A Barbato), Perugia (C Cavallini, C Borgioni), Pistoia (G Seghieri, F Cipollini, E Arcangeli), Poggibonsi (W Boddi, C Palermo, F Savelli), Pozzilli (G Lembo, C Vecchione), Ragusa (L Malatino, P Belluardo), Reggio Calabria (C Zoccali, D Leonardis, F Mallamaci), Roma San Camillo (A Lacchè, C Gentile), Roma San Giovanni (A Boccanelli, GF Mureddu), Roma San Filippo Neri (M Santini, F Colivicchi, S Ficili), Roma CTO (M Uguccioni, C Nardozi, A Tedeschi), Sacile (G Martin, G Zanata), San Daniele del Friuli (L Mos, V Dialti, S Martina), San Pietro Vernotico (S Pede, A Renna), Sassari (A Ganau, G Farina), Scilla (E Tripodi, B Miserrafiti, R Scali), Siracusa (M Stornello, E Valvo), Terni (M Bernardinangeli, G Proietti), Thiesi (G Poddighe), Todi (B Biscottini, R Panciarola, A Boccali), Torino (F Veglio, F Rabbia, M Caserta), Trebisacce (M Chiatto), Trento (C Stefenelli, G Cioffi, G Bonazza) and Viterbo (EV Scabbia, A Achilli, D Bottoni).

Definition of secondary outcome events

Myocardial infarction (MI) is defined as follows:

  1. 1)

    Q-wave or ST-elevation MI: new significant Q-wave (>0. 04 s duration or 3 mm in depth and loss in height of ensuing R wave or new significant R waves in V1–V2) in at least 2 leads on the standard 12-lead ECG. ST elevation is defined as 0.1 mV new ST elevation of 0.1 mV in peripheral leads or 0.2 mV in precordial leads. New onset left bundle branch block during MI is equivalent to a ‘Q-Wave MI’. There must be at least one of the following criteria: (1) typical chest pain, or increase of CK-MB above the upper limit of normal within 36 h of onset of acute symptoms, (2) serum glutamic oxaloacetic transaminase or LDH at least twice the laboratory upper limit and (3) elevated troponin T or I level above the normal laboratory range.

  2. 2)

    ‘Non-Q-wave’ or ‘non-ST elevation’ MI: new and persistent (>24 h) ST-segment or T wave changes in addition to cardiac enzymes/markers elevation (see above) and/or typical symptoms of chest pain.

  3. 3)

    MI without significant ECG changes: typical symptoms with significant elevation of cardiac enzymes (see above).

‘Stroke’ is defined by acute focal neurological deficit thought to be of vascular origin and signs or symptoms lasting >24 h. On the basis of symptoms and laboratory tests (computed tomography/magnetic resonance imaging) and/or necropsy results, stroke is classified as (1) definite or probable ischaemic stroke or (2) definite or probable haemorrhagic stroke or (3) sub-arachnoid haemorrhage or (4) uncertain or unknown stroke.

‘Transient ischaemic attack’ is defined by focal neurological or monocular defect with associated symptoms lasting <24 h and thought to be due to occlusive (embolic or thrombotic) vascular origin.

‘Atrial fibrillation’ is defined by absence of P waves before each QRS complex on the surface ECG with irregular atrial electrical activity and f waves varying in size, shape and timing. All cases of AF must be documented by ECG tracings for adjudication. Paroxysmal AF is defined by a single or multiple occurrence of AF that resolved spontaneously or by treatment.

‘Sudden cardiac death’ is defined by a sudden, unexpected and witnessed death that occurred within 1 h from onset of symptoms, in the absence of any known relation with traumatic or violent causes.

‘Death due to other cardiovascular causes’ is defined by a cardiovascular death different from myocardial infarction or stroke (for example, death due to heart failure or aortic dissection).

‘Congestive heart failure’ NYHA stage III or IV is defined by congestive heart failure with dyspnoea induced by a lesser than usual physical activity (stage III) or at rest (stage IV) associated with hospitalization and treatment of the patient.

‘Angina with objective evidence of myocardial ischaemia’ is defined by new onset chest pain associated with objective evidence of myocardial ischaemia at ECG, radionuclide study or stress echocardiography, or with angiographic evidence of at least 50% stenosis in >= 2 major epicardial vessels.

‘Peripheral occlusive arterial disease’ is defined by intermittent claudication associated with angiographic or ecographic evidence of arterial stenosis >60%.

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Cardio-Sis Study Group (see appendix). Randomized study of traditional versus aggressive systolic blood pressure control (Cardio-Sis): rationale, design and characteristics of the study population. J Hum Hypertens 22, 243–251 (2008). https://doi.org/10.1038/sj.jhh.1002313

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