What is Coveram (Perindopril/Amlodipine)?
Coveram is a fixed-dose combination antihypertensive medication containing perindopril (an ACE inhibitor) and amlodipine (a dihydropyridine calcium channel blocker), indicated for the treatment of hypertension and stable coronary artery disease. 1
Composition and Mechanism
- Perindopril blocks the renin-angiotensin system by inhibiting angiotensin-converting enzyme, reducing vasoconstriction and aldosterone secretion 1
- Amlodipine causes direct arterial vasodilation by blocking calcium channels in vascular smooth muscle 1
- The two agents work synergistically through complementary mechanisms, providing more efficient blood pressure reduction than either component alone 2, 3
Clinical Indications
Primary indications include:
- Hypertension requiring dual-agent therapy to achieve blood pressure targets 1, 4
- Stable coronary artery disease with or without hypertension 1, 2
- Patients with uncontrolled hypertension on monotherapy who need combination treatment 4
Evidence Base for Cardiovascular Protection
The combination strategy of ACE inhibitor plus calcium channel blocker is strongly supported by major cardiovascular outcome trials:
- ASCOT trial demonstrated that amlodipine-based therapy (with perindopril added as needed) reduced total cardiovascular events by 14% compared to atenolol-based therapy in diabetic patients (HR 0.86,95% CI 0.76-0.98), including a 25% reduction in fatal and nonfatal strokes 5
- ACCOMPLISH trial showed that benazepril plus amlodipine reduced major cardiovascular events by 20% compared to benazepril plus hydrochlorothiazide (HR 0.80,95% CI 0.72-0.90), though no specific stroke reduction was observed 5
Available Formulations and Dosing
- Multiple dose combinations are available, allowing titration of each component according to individual patient needs 1
- Typical dosing ranges from perindopril 3.5-14 mg combined with amlodipine 2.5-10 mg, taken once daily 3
- The fixed-dose combination improves medication adherence by reducing pill burden compared to taking separate tablets 1, 6
Efficacy Profile
- Perindopril/amlodipine combination provides significantly greater blood pressure reduction than either monotherapy alone 3
- The combination appears more effective than up-titration strategies using valsartan-based regimens 3
- Effective blood pressure control is achieved with good tolerability in both clinical trials and real-world observational studies 6
Tolerability and Adverse Effects
Common adverse events include:
- Peripheral edema (dose-dependent, but attenuated when ACE inhibitor is combined with calcium channel blocker) 7, 3
- Cough (typical ACE inhibitor side effect) 3
- Headache and dizziness 3
Important advantage: The incidence of peripheral edema is numerically lower with the perindopril/amlodipine combination compared to amlodipine monotherapy, likely due to the ACE inhibitor's effect on venous tone 3
Role in Treatment Algorithms
- Combination therapy is specifically indicated when systolic blood pressure exceeds target by >20 mmHg or diastolic by >10 mmHg 4
- Particularly appropriate for patients with diabetes mellitus (target <130/80 mmHg), target organ damage, or cardiovascular disease 4
- The ACE inhibitor component provides additional benefits in diabetic patients with albuminuria or renal insufficiency 5
Clinical Advantages
- Simplified management: Addresses both blood pressure control and coronary artery disease protection in a single tablet 2
- Improved compliance: Reduces pill burden, which may improve adherence and lead to better blood pressure control and clinical outcomes 6
- Complementary mechanisms: The combination improves fibrinolytic function and reduces secondary effects compared to higher doses of monotherapy 2