Efficacy and tolerability of the perindopril/indapamide combination therapy for hypertension: the PRIMUS study

Background: Tight blood pressure (BP) control is required to reduce cardiovascular morbidity and mortality. Objective: To evaluate the efficacy and tolerability of the first line combination perindopril/indapamide in hypertension in daily practice. Design and methods: In this prospective, open-label, observational trial, 1892 general practitioners in Germany recruited patients with hypertension (n = 8023; mean age 59.6 years, 48.1% males, body mass index 27.6 kg/m(2), systolic BP >= 140 mmHg and/or diastolic BP >= 90 mmHg) between October 2002 and December 2004. Patients received perindopril 2 mg/indapamide 0.625 mg for 12 weeks. BP measured in the general practice setting, safety, and tolerability were evaluated after 4 and 12 weeks. Results.-At baseline, most patients had moderate to severe hypertension (78%); initial BP was 164.6/95.8 mmHg. At inclusion, 38% of the patients were newly diagnosed hypertensives (mean BP 166.1/97.2 mmHg) and 58% of patients had uncontrolled BP despite preexisting antihypertensive treatment (163.5/94.9 mmHg). Previous treatment consisted of beta-blockers (49.5%), ACE inhibitors (36.4%), calcium-antagonists (29.3%), diuretics (28.8%), AT-I receptor antagonists (7.1%), and other treatments (8.1%). In the entire study cohort, treatment with perindopril/indapamide significantly decreased systolic BP (27.9 mmHg), diastolic BP (13.7 mmHg), and pulse pressure (14.2 mmHg), compared with baseline (p < 0.0001); 96% of patients responded to treatment and in 50% of patients BP was normalized (< 140/90 mmHg). Treatment dose was doubled in 9.5% of patients. Similar results were found in various subgroup analyses (newly diagnosed patients, the elderly, and patients with isolated systolic hypertension, additional cardiovascular risk factors, associated diseases, or target organ damage). The most frequent adverse events (< 1% of patients) were dry cough and nausea. Conclusions: The open-label, observational study PRIMUS, extends the existing evidence that the first line combination treatment of hypertension with perindopril/indapamide is effective, safe, and well tolerated in a representative cross-section of patients with newly diagnosed or pretreated but uncontrolled hypertension in daily practice.